Gastroenterology Research and Practice最新文献

Background and Aim: Superficial nonampullary duodenal epithelial tumors (SNADETs) that are pathologically classified as gastric-type might manifest a more aggressive behavior than the intestinal type. However, the details of their histologic and genetic features remain unclear because of their rarity. This study was aimed at identifying clinicopathological findings and early genomic events in gastric-type SNADETs treated with endoscopic resection. Methods: We retrospectively analyzed 204 patients with SNADETs between January 2011 and September 2020. Immunohistochemical analysis for β-catenin and targeted exome sequence analysis of 50 cancer-related genes using next-generation sequencing were performed for the representative cases. Results: Among the 204 SNADETs cases, only nine (4.4%) were gastric type; the remaining 195 cases were intestinal type. Among the gastric-type tumors, seven were adenomas and two were adenocarcinomas, whereas only three of the 195 intestinal-type tumors were adenocarcinomas. Nuclear expression of β-catenin was observed in three of the nine (33%) gastric-type tumors and in eight of the 10 (80%) intestinal-type tumors. The most prevalent abnormality among the 50 genes tested in gastric-type tumors was GNAS mutation (89%), whereas that in intestinal-type tumors was APC mutation (67%). All gastric-type adenocarcinomas had GNAS mutations as well as adenomas, while APC mutations were absent in intestinal-type adenocarcinomas and present in most adenomas. Conclusions: GNAS mutations are more common in gastric-type SNADETs than in the intestinal type. As GNAS mutations are continuously present from adenoma to adenocarcinoma, resection at the adenoma stage is desirable.

Background and Study Aim: Changrun Formula (CRF) is a representative traditional Chinese medicine prescription for functional constipation (FC). However, the mechanism by which CRF alleviates FC remains unclear. Therefore, this study aimed to investigate the therapeutic mechanism of CRF in an FC rat model. Material and Methods: A total of 72 healthy SD rats were selected and randomly divided into six groups: the blank group, model group, hemp seed pill (HSP) group, high-dose CRF group, medium-dose CRF group, and low-dose CRF group. Except for the blank group, all the other groups were administered compound diphenoxylate via oral gavage to establish the FC rat model with impaired intestinal motility. The expression of genes related to intestinal motility in the colon tissues of rats was analyzed using Western blotting and real-time PCR. The effect of CRF on isolated colonic smooth muscle was assessed through electrophysiological analysis. Results: Compared with the blank group, the other groups exhibited a longer time to expel the first black stool and a reduced number of fecal particles within 6 h, confirming the successful establishment of the FC rat model. Furthermore, the expressions of HCN1, c-kit, and SP in the colon tissue of the model group were significantly decreased, while the expression level of VIP was significantly increased. HCN1 was found to colocalize with c-kit, SP, and VIP. Treatment of CRF (high and medium doses) significantly increased the expressions of c-kit, SCF, HCN1, and HCN2, enhanced the contractile movement of colonic smooth muscle, and improved muscle tension. Conclusions: CRF likely improves intestinal motility by targeting HCN1 and HCN2 ion channels and the SCF/c-kit signaling pathway, thereby alleviating FC symptoms in rats.

Purpose: Fecal calprotectin (FC) is a Crohn's disease (CD) biomarker, although the impact of disease duration on its accuracy remains unclear. This study was aimed at investigating the effects of CD disease duration on FC. Methods: In this prospective, single-center, cross-sectional study, we performed 113 endoscopies and biomarker measurements. Endoscopy results were assessed using the simple endoscopic score for Crohn's disease (SES-CD), with an SES-CD ≤ 2 defined as endoscopic remission (ER). Cohort 1 was divided into short-term and long-term disease groups. The associations of the SES-CD with C-reactive protein and FC were analyzed. Results: The correlation coefficient of FC and the SES-CD was 0.670 for all cases. In Cohort 1, the correlation coefficient of FC and the SES-CD was > 0.670 for all subgroups of the short-term disease group (≤ 20 years). The correlation coefficient of FC and CD was < 0.670 for all subgroups of the long-term disease group (> 20 years). In Cohort 2, the correlation coefficients were > 0.670 (0.808) for the 0-4-year disease group and < 0.670 for the 5-14- and 15-40-year disease groups. The receiver-operating characteristic analysis performed to predict ER of all cases resulted in an area under the curve (AUC) of 0.8443, with large AUCs of 0.907, 0.816, and 0.770 observed for the 0-4-, 5-14-, and 15-40-year disease groups, respectively. Conclusions: FC was affected by CD duration, and it may be a useful biomarker of CD, especially in patients with a short disease duration.

A potential contributing factor in the development of various metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) could be oxidative stress and the production of reactive oxygen radicals. A high level of lipid peroxidation, including oxidative stress, can cause irreversible effects. We investigated the consequences of NAFLD on the reducing power of the liver in patients through plasma antioxidant capacity using screen-printed electrodes (SPEs). The study includes a total of 67 patient's population with steatosis (n = 29) and steatohepatitis (n = 38). Anodic current intensity (la), anodic wave area (S), and the biological sample oxidation potentials can be determined via cyclic voltammetry (CV) analysis. The enzyme glutathione peroxidase (GPx) and products of oxidative damage such as malondialdehyde (MDA), advanced glycation-end product (AGE), total status of oxidants (TOS), nitric oxide (NO), and cytokines analysis (qRT-PCR) of key mediators such as PNPLA3 in lipid metabolism, TIMP1 in fibrosis, and proinflammatory cytokines like NF-κB, TNF-α, and IL-6, which are crucial for understanding NAFLD progression were recorded to further validate the CV obtained results along with and morphological changes through scanning electron microscope (SEM). The developed method measured oxidative stress with an error of less than 1.3% in human plasma samples, wherein the steatohepatitis caused a spike modification in the anodic current AC₅₂₀ and AC₉₇₂ (p < 0.01) compared to healthy humans. The presented electroanalytical methodology could be widely used for easy and rapid subjects' disease status detection. In addition to monitoring the response of subjects to treatment and providing nutritional supplements, these results may also be used for screening specific populations.

Background: In March 2020, the severe acute respiratory distress syndrome coronavirus 2 (COVID-19) became a worldwide pandemic. Recently, it has been shown that direct entry of this virus in the gastrointestinal (GI) epithelial cells causes tissue damage and the use of anticoagulants increases the risk of GI bleeding. These pose real concerns for the gastroenterologists concerning the mortality, overall incidence, and management of upper GI bleeding in SARS-CoV-2-positive patients. Methods: This retrospective study includes patients 18 years or older admitted to our health system with an upper GI bleed (UGB). Patients with possible UGB, endoscopy, and SARS-CoV-2-positive testing (n = 587) formed the initial cohort. In-depth data were collected for symptoms, medications, source of bleeding, and interventions for subsets of test and control subjects. Results: Duodenal ulcer was the most common etiology for GI bleeding in SARS-CoV-2-positive patients, while esophagitis was the most common etiology in control subjects. SARS-CoV-2-positive patients had significant progressive anemia and had to be given more blood transfusions, steroids, proton pump inhibitors, and immunosuppressants. In-hospital mortality was greater in the experimental group (12.8%) than in the control group (5.1%). Furthermore, the SARS-CoV-2-positive patients had more therapeutic interventions compared to the SARS-CoV-2-negative patients. Nearly one-quarter of all patients had an endoscopy over 48 h after bleeding was observed. Conclusions: Healthcare providers should be aware of the greater therapeutic needs of SARS-CoV-2-positive patients with UGB. Our data helps shed light on the relationship between SARS-CoV-2 and GI bleeding due to SARS-CoV-2-related tissue damage and treatment affecting the GI tract.

Background: Pancreatic cancer is very susceptible to metastasis with a high mortality. Neutrophil extracellular traps (NETs) have been reported to be associated with poor prognosis in patients suffering from pancreatic cancer. However, the underlying mechanisms by which NETs facilitate cancer progression remain poorly understood. Methods: The expression of NETs was assessed in pancreatic cancer tissues and plasma samples from patients. Neutrophils were isolated from the blood of individuals diagnosed with pancreatic cancer to evaluate NETs formation. The impact of NETs on the progression of pancreatic cancer cells was investigated, along with a series of experiments aimed at elucidating the interaction mechanisms between neutrophils and cancer cells. Results: Pancreatic cancer samples had higher levels of NETs, and NETs formation was intensified in neutrophils derived from patients. NETs significantly promoted both migration and invasion capabilities in pancreatic cancer cells. Furthermore, the stimulator of interferon genes (STING) signaling pathway was stimulated to produce interleukin-8 (IL-8), which subsequently recruited more neutrophils and mediated further formation of NETs. Conclusions: Our data indicate a NETs-cancer aggressive crosstalk in pancreatic cancer. Specifically, NETs stimulate tumor cells to secrete IL-8, thereby promoting NETosis within the tumor microenvironment. Consequently, NETs may be a key target for pancreatic cancer treatment.

Background: The use of adjuvant chemotherapy in patients with stage T3N0 rectal cancer following total mesorectal excision (TME) is debated. This study is aimed at investigating the clinical significance of negative lymph node (NLN) counts in patients with T3N0 rectal cancer, particularly in relation to adjuvant chemotherapy. Methods: This retrospective analysis examined 311 patients with T3N0 rectal cancer who underwent radical resection at the Sixth Affiliated Hospital of Sun Yat-sen University between August 2014 and December 2021. The optimal cutoff for NLN counts was determined using receiver operating characteristic (ROC) curves. Clinicopathological characteristics and clinical outcomes were compared between the high and low NLN groups. Overall survival (OS) and disease-free survival (DFS) were used to evaluate the efficacy of adjuvant chemotherapy. Results: The optimal cutoff for NLNs was 21. Of the 311 patients, 141 were categorized into the high NLN group and 170 into the low NLN group. Patients with NLNs ≥ 21 had significantly better 5-year OS (99.3% vs. 88.2%, p < 0.05) and 5-year DFS (92.2% vs. 79.4%, p < 0.05) compared to those with low NLNs. Multivariate Cox analysis revealed that NLN count was an independent prognostic factor for OS (hazard ratio (HR) = 0.078, 95% confidence interval (CI): 0.011-0.582, p = 0.013) and DFS (HR = 0.417, 95% CI: 0.213-0.815, p = 0.011). Subgroup analysis indicated that adjuvant chemotherapy significantly improved OS (p < 0.05) and DFS (p < 0.05) in the low NLN group. Conclusion: NLN count is an independent prognostic factor in patients with T3N0 rectal cancer. Patients with low NLN counts (NLN < 21) may benefit from adjuvant chemotherapy.

Purpose: This study is aimed at investigating the role of key molecular elements involved in pyroptosis in liver injury caused by exertional heat stroke (EHS). Methods: We established a model of EHS-induced liver injury in Sprague-Dawley rats, with a control group (receiving no treatment) for comparison and 12 rats in each group. Alanine transaminase (ALT) and aspartate transaminase (AST) levels in the blood were detected. Interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) levels were assessed using enzyme-linked immunosorbent assays (ELISA). Pathological changes in liver tissue were examined by hematoxylin and eosin (H&E) staining. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect mRNA and protein expression levels of Caspase-1 and Gasdermin D. Results: Compared to the control group, the liver tissue of the EHS group showed congestion in hepatic sinusoids, hepatocyte edema, eosinophilic changes, necrosis, and infiltration of inflammatory cells. ALT and AST levels in the EHS group were significantly higher than those in the control group (p < 0.05). The mRNA expressions of Caspase-1, Gasdermin D, IL-1β, and IL-18 were significantly increased in the EHS group compared to the control group (p < 0.001). The protein expressions of Caspase-1, cleaved Caspase-1, Gasdermin D, and cleaved Gasdermin D were significantly increased in the EHS group. Conclusion: These findings indicated that hepatic pyroptosis plays an important role in EHS-induced liver injury.

Background and Aims: The pandemic of coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide, including the pediatric inflammatory bowel disease (PIBD) patients. As no study has investigated the susceptibility and disease course of COVID-19 in PIBD patients after the end of zero-COVID policy in China, we conducted a retrospective cross-sectional study in our center. Methods: A cross-sectional survey enrolling PIBD patients has been completed by online survey, phone, and face-to-face assessment. The demographic data, epidemiological characteristics, clinical manifestations, treatment, and prognosis of the patients were analyzed. Results: PIBD patients represented 55.45% (56/101) of SARS-CoV-2-positive cases between December 1st 2022 and January 31st 2023; 67.86% were male; the mean age was 11.15 ± 3.92 years old. Among the SARS-CoV-2-positive cases, three patients (5.36%) were asymptomatic, and 53 patients (94.64%) had mild symptoms. The main symptoms were fever (92.86%), cough (69.64%), nasal congestion or running nose (35.71%), and sore throat (33.93%). No severe case or deaths were reported. All patients recovered from COVID-19 symptoms within 1 week. We found no significant association between the type of inflammatory bowel disease (IBD) (Crohn's disease, ulcerative colitis, and unclassified) and SARS-CoV-2 infection rates, nor did we observe any correlation between different treatments and the risk of infection. Fifty-one patients were reported to be in close contact with persons confirmed with COVID-19 infection, and out of them, 36 patients test positive for SARS-CoV-2, which is significantly higher than that in patients without exposure to COVID-19 (70.59% vs. 33.33%, p = 0.002). A total of 10 patients were underweight, of which nine patients tested positive for COVID-19 (90% vs. 51.65%, p = 0.048). Meanwhile, unvaccinated patients were also found to be more susceptible to SARS-CoV-2 than vaccinated patients (70.97% vs. 48.48%, p = 0.049). The multivariable analysis showed that patients with moderate/severe activity of IBD were associated with an increased risk of SARS-CoV-2 infection (odds ratio (OR), 1.12; 95% confidence interval (CI), 1.13-8.33, p = 0.028). Conclusions: The incidence of SARS-CoV-2 infection in our center of PIBD patients during the Omicron pandemic was 55.45%. No severity or death case was observed. The incidence was higher in underweight and unvaccinated IBD children. Patients with moderate/severe activity of IBD were at a higher risk of SARS-CoV-2 infection.

Goal: This study is aimed at comparing the clinical characteristics and histological types of symptomatic and asymptomatic patients with heterotopic gastric mucosa in the upper esophagus (HGMUE) and exploring the factors influencing the occurrence and severity of laryngopharyngeal reflux (LPR) symptoms in these patients. Background: HGMUE is a potential cause of LPR symptoms. Study: This retrospective analysis evaluated 70 patients with HGMUE using a detailed questionnaire. Clinical, histological, high-resolution manometry, and 24-h pH impedance monitoring data were compared between symptomatic (n = 49) and asymptomatic (n = 21) patients. Results: The diameter of HGMUE was significantly larger in the symptomatic group (p < 0.05), and the incidence of LPR symptoms increased with larger diameter grades; male patients were more likely to have LPR symptoms. The incidence of LPR symptoms varied significantly across histological classifications, being highest in patients with the fundic type (χ ² = 6.64, p < 0.05). Binary logistic regression analysis identified sex and histological type as risk factors for LPR symptoms, with odds ratios of 8.996 (95% confidence interval (CI): 1.350-59.962) and 8.493 (95% CI: 1.486-48.522), respectively. The mean nocturnal baseline impedance (MNBI) in the upper esophagus was significantly lower in the symptomatic group (1676.82 ± 739.09 Ω vs. 2441.01 ± 604.11 Ω; p < 0.05). Clinical and demographic characteristics did not significantly affect the severity of LPR symptoms. Conclusion: The diameter, histological type, and sex of patients are risk factors for the occurrence of LPR symptoms in patients with HGMUE. More attention should be paid to patients with these factors. The MNBI is an effective indicator of the symptoms and treatment.